Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome

Autor: Federica Plano, Emilia Gigliotta, Anna Maria Corsale, Mojtaba Shekarkar Azgomi, Carlotta Santonocito, Manuela Ingrascì, Laura Di Carlo, Antonino Elia Augello, Maria Speciale, Candida Vullo, Cristina Rotolo, Giulia Maria Camarda, Nadia Caccamo, Serena Meraviglia, Francesco Dieli, Sergio Siragusa, Cirino Botta
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 10, p 8852 (2023)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms24108852
Popis: Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromolecules, which contributes to ROS production and cellular damage. In this study, we showed that ferritin increases from indolent to active gammopathies and that patients with low serum ferritin had longer first line PFS (42.6 vs. 20.7 months and, p = 0.047, respectively) and OS (NR vs. 75.1 months and p = 0.029, respectively). Moreover, ferritin levels correlated with systemic inflammation markers and with the presence of a specific bone marrow cell microenvironment (including increased MM cell infiltration). Finally, we verified by bioinformatic approaches in large transcriptomic and single cell datasets that a gene expression signature associated with ferritin biosynthesis correlated with worse outcome, MM cell proliferation, and specific immune cell profiles. Overall, we provide evidence of the role of ferritin as a predictive/prognostic factor in MM, setting the stage for future translational studies investigating ferritin and iron chelation as new targets for improving MM patient outcome.
Databáze: Directory of Open Access Journals
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